UNIT -I Ms.Smita

Shukla

All cells must know how to respond to their environment. They must be

able to divide, grow, secrete, synthesize, degrade, differentiate, cease

growth, and even die when the appropriate signal is given. This signal

invariably is a molecule which binds to a receptor, typically on the cell

surface. (Exceptions include light transduction in retinal cells when the

signal is a photon, and lipophilic hormones which pass through the

membrane.) Binding is followed by shape changes in transmembrane

protein receptors which effectively transmit the signal into the

cytoplasm.

To survive, an organism must constantly adjust its internal state to changes

in the environment. To track environmental changes, the organism must

receive signals. These may be in the form of chemicals, such

as hormones or nutrients, or may take another form, such as light, heat, or

sound.

A signal itself rarely causes a simple, direct chemical change inside the cell.

Instead, the signal sets off a chain of events that may involve several or

even dozens of steps. The signal is thereby transduced, or changed in form.

Signal transduction refers to the entire set of pathways and interactions by

which environmental signals are received and responded to by single cells.

Signal transduction systems are especially important in multicellular

organisms, because of the need to coordinate the activities of hundreds to

trillions of cells. Multicellular organisms have developed a variety of

mechanisms allowing very efficient and controlled cell-to-cell

communication.

Though we take it for granted, it is actually astonishing that our skin, for

example, continues to grow at the right rate to replace the continuous loss

of its surface every day of our lives. This tight regulation is found in every

tissue of our body all of the time, and when this fine control breaks down,

UNIT -I Ms.Smita

Shukla

cancer may be the result. Clearly the molecular mechanisms behind this

astounding level of control must be powerful, versatile, and sophisticated.

Signals, Receptors, and Cascades

The signals that cells use to communicate with one another are often small

amino acid chains, called peptides. Depending on the cell type that releases

them and the effect they have on the target cell, they may be called

hormones, growth factors, neuropeptides, neurotransmitters, or

cytokines. Other small molecules can also be signals, such as amino acids

and steroids such as testosterone. External signals such as odorants and

tastes can be carried to us in the atmosphere or in the fluids of our food and

drinks. Stretch, pressure, and other mechanical effects as well as heat, pain,

and light can also act as signals.

Given the huge variety of signals to which a cell is exposed, how does it

know which to respond to? The answer is that signals are received by

protein receptors made by the cell, and a cell is sensitive only to those

signals for which it has made receptors. For instance, every cell in the body

is exposed to estrogens circulating in the blood, but only a subset of them

make estrogens receptors, and are therefore sensitive to its influence.

Chemical signals such as hormones bind to their receptors, usually at the

surface of the cell (the plasma membrane), but sometimes within the cell.

This causes a conformation (shape) change in the receptor. The

conformation change typically alters the ability of the receptor to bind to

another molecule in the cell, modifying that molecule's conformation, or

triggering other actions.

This sequence of events triggered by the signal-receptor interaction is

called a transduction cascade. A transduction cascade involves a network

of enzymes that act on one another in specific ways to ultimately generate

precise and appropriate responses.

UNIT -I Ms.Smita

Shukla

The Importance of Phosphorylation &

Dephosphorylation

After a signal is received, signal transduction involves altering the

behaviour of proteins in the cascade, in effect turning them on or off

like a switch. Adding or removing phosphates is a fundamental

mechanism for altering the shape, and therefore the behaviour, of a

protein. Phosphorylation may open up an enzyme's active site, allowing

it to perform chemical reactions, or it may frequently generate a binding

site allowing a specific interaction (may make a bulge in one side

preventing the protein from fitting together) with a molecular partner.

Enzymes that add phosphate groups to other molecules are called kinases,

and the molecules the enzymes act on are called substrates.

Protein kinases are a family of enzymes that use ATP to add phosphate

groups on to other proteins, thereby altering the properties of these

substrate proteins.

Protein kinases themselves are frequently turned on or off by

phosphorylation performed by other protein kinases; thus a kinase can be

both enzyme and substrate.

Membrane receptors transfer information from the

environment to the cell's interior.

A few nonpolar signal molecules such as estrogens and other steroid

hormones are able to diffuse through the cell membranes and, hence, enter

the cell. Once inside the cell, these molecules can bind to proteins that

interact directly with DNA and modulate gene transcription.

Thus, a chemical signal enters the cell and directly alters gene-expression

patterns.

However, most signal molecules are too large and too polar to pass

through the membrane, and no appropriate transport systems are present.

UNIT -I Ms.Smita

Shukla

Thus, the information that signal molecules are present must be transmitted

across the cell membrane without the molecules themselves entering the

cell. A membrane-associated receptor protein often performs the function

of information transfer across the membrane.

Such a receptor is an intrinsic membrane protein that has both

extracellular and intracellular domains. A binding site on the extracellular

domain specifically recognizes the signal molecule (often referred to as

the ligand). Such binding sites are analogous to enzyme active sites except

that no catalysis takes place within them.

The interaction of the ligand and the receptor alters the tertiary or

quaternary structure of the receptor, including the intracellular domain.

These structural changes are not sufficient to yield an appropriate

response, because they are restricted to a small number of receptor

molecules in the cell membrane.

The information embodied by the presence of the ligand, often called

the primary messenger, must be transduced into other forms that can

alter the biochemistry of the cell.